bimosiamose   Click here for help

GtoPdb Ligand ID: 9049

Synonyms: compound 15e [PMID: 9544210] [4] | TBC 1269 | TBC-1269 | TBC1269
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Bimosiamose is a synthetic pan-selectin antagonist [4] being investigated as a novel anti-inflammatory agent, primarily for controlling allergic respiratory diseases [7,9], but it has also been reported to provide benefit in ischemia/reperfusion injury [1-2,5-6,8]. The primary role of selectin inhibitors appears to be disruption of early events in the migration process (possibly mediated through E-selectin [3]), thereby inhibiting their eventual extravasation from blood to the inflammed tissue.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 10
Rotatable bonds 19
Topological polar surface area 273.36
Molecular weight 862.34
XLogP 5.95
No. Lipinski's rules broken 4
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Canonical SMILES OCC1OC(Oc2ccc(cc2c2cccc(c2)CC(=O)O)CCCCCCc2ccc(c(c2)c2cccc(c2)CC(=O)O)OC2OC(CO)C(C(C2O)O)O)C(C(C1O)O)O
Isomeric SMILES OC[C@H]1O[C@H](Oc2ccc(cc2c2cccc(c2)CC(=O)O)CCCCCCc2ccc(c(c2)c2cccc(c2)CC(=O)O)O[C@H]2O[C@H](CO)[C@H]([C@@H]([C@@H]2O)O)O)[C@H]([C@H]([C@@H]1O)O)O
InChI InChI=1S/C46H54O16/c47-23-35-39(53)41(55)43(57)45(61-35)59-33-15-13-25(19-31(33)29-11-5-9-27(17-29)21-37(49)50)7-3-1-2-4-8-26-14-16-34(60-46-44(58)42(56)40(54)36(24-48)62-46)32(20-26)30-12-6-10-28(18-30)22-38(51)52/h5-6,9-20,35-36,39-48,53-58H,1-4,7-8,21-24H2,(H,49,50)(H,51,52)/t35-,36-,39-,40-,41+,42+,43+,44+,45+,46+/m1/s1
1. Anaya-Prado R, Pérez-Gomez N, Toledo-Pereyra LH, Walsh J, Jordan J, Ward PA. (2008)
Small molecule selectin inhibitor in global cerebral ischemia and controlled hemorrhagic shock.
J Trauma, 65 (3): 678-84. [PMID:18784584]
2. Calvey CR, Toledo-Pereyra LH. (2007)
Selectin inhibitors and their proposed role in ischemia and reperfusion.
J Invest Surg, 20 (2): 71-85. [PMID:17454392]
3. Hicks AE, Abbitt KB, Dodd P, Ridger VC, Hellewell PG, Norman KE. (2005)
The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo.
J Leukoc Biol, 77 (1): 59-66. [PMID:15466915]
4. Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. (1998)
Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).
J Med Chem, 41 (7): 1099-111. [PMID:9544210]
5. Nemoto T, Burne MJ, Daniels F, O'Donnell MP, Crosson J, Berens K, Issekutz A, Kasiske BL, Keane WF, Rabb H. (2001)
Small molecule selectin ligand inhibition improves outcome in ischemic acute renal failure.
Kidney Int, 60 (6): 2205-14. [PMID:11737594]
6. Onai Y, Suzuki J, Nishiwaki Y, Gotoh R, Berens K, Dixon R, Yoshida M, Ito H, Isobe M. (2003)
Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion injury.
Eur J Pharmacol, 481 (2-3): 217-25. [PMID:14642789]
7. Romano SJ, Slee DH. (2001)
Targeting selectins for the treatment of respiratory diseases.
Curr Opin Investig Drugs, 2 (7): 907-13. [PMID:11757789]
8. Toledo-Pereyra LH, Lopez-Neblina F, Reuben JS, Toledo AH, Ward PA. (2004)
Selectin inhibition modulates Akt/MAPK signaling and chemokine expression after liver ischemia-reperfusion.
J Invest Surg, 17 (6): 303-13. [PMID:15764497]
9. Vanderslice P, Biediger RJ, Woodside DG, Berens KL, Holland GW, Dixon RA. (2004)
Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD.
Pulm Pharmacol Ther, 17 (1): 1-10. [PMID:14643165]
10. Watz H, Bock D, Meyer M, Schierhorn K, Vollhardt K, Woischwill C, Pedersen F, Kirsten A, Beeh KM, Meyer-Sabellek W et al.. (2013)
Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD.
Pulm Pharmacol Ther, 26 (2): 265-70. [PMID:23257347]